Biomedical subjects
Publications and source records attributed to D Jurkovic.
In 15 women undergoing therapeutic termination of pregnancy (8-13 weeks), the median concentration of relaxin was 1000 ng/l in maternal serum, 122 ng/l in coelomic fluid and 9 ng/l in amniotic fluid. Its presence in coelomic fluid suggests that relaxin may be present in the fetal circulation and thus be able to influence embryonic development during the period of organogenesis.
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Levels of human chorionic gonadotrophin (hCG) and of its free alpha and beta subunits were measured using specific immunoradiometric assays in exocoelomic fluid (ECF) and maternal serum (MS) collected from five pregnant women at 6.6-8 weeks of gestation. Mean levels of hCG and its free subunits were significantly (P < 0.001) higher in ECF than in MS: 3.5-fold for hCG, 600-fold for free alpha hCG and 38-fold for beta hCG. There was no correlation between either hCG levels or levels of its free subunits in ECF and MS. On a molar basis, the quantity of free alpha hCG subunit expressed as a percentage of the total (free+combined) amount was 83% in ECF and 2.7% in MS (P < 0.001). The amount of free beta hCG subunit as a percentage of the total was 22% in ECF and 3.5% in MS (P < 0.001). The ratio of the total amounts of alpha- and beta hCG subunits amounted to 4.6 in ECF and 0.99 in MS (P < 0.001). The heterogeneity of hCG was further investigated by polyacrylamide gel electrophoresis followed by immunoblotting. Several bands with molecular mass ranging from 42 to 57 kDa, corresponding to hCG dimers, were immunodetected in ECF and MS with anti-alpha hCG and anti-beta hCG monoclonal antibodies. A free 35 kDa beta hCG immunoreactive band was found in ECF and MS. A free alpha hCG immunoreactive band was observed at 23 kDa in ECF and at 21 kDa in MS. These findings suggest that the exocoelomic cavity is a reservoir where hCG and its subunits produced by trophoblast accumulate directly.(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVE: To investigate the iron distribution between the maternal and embryonic compartments in the first trimester of pregnancy. METHODS: Coelomic and amniotic fluids (AF) and maternal serum were collected from 36 apparently normal pregnancies at 7-13 weeks of gestation. Iron, transferrin, ferritin, and lactoferrin were measured in all samples. Iron concentrations were also measured in placental villi, liver, gut, and brain samples collected from two embryos. RESULTS: Significantly (median value) lower iron and transferrin levels and higher levels of ferritin were found in the coelomic fluid (iron 4.8 mumol/L; transferrin 0.22 g/L) than in maternal serum (iron 21 mumol/L; transferrin 2.5 g/L). The AF contained significantly lower levels of iron and ferritin (iron less than 1.8 mumol/L; ferritin 2.0 micrograms/L) than both coelomic fluid (iron 4.8 mumol/L; ferritin 287 micrograms/L) and maternal serum (iron 21 mumol/L; ferritin 49 micrograms/L). Transferrin was undetectable (less than 0.08 g/L) in AF samples, and lactoferrin was undetectable (less than 2 micrograms/mL) in both embryonic fluids. The iron concentration in the coelomic fluid increased significantly (P < .001) with advancing gestation (iron at 7-9 weeks 3.8 mumol/L; 9.1-11 weeks 5.9 mumol/L). There was a nonsignificant correlation between coelomic fluid and maternal serum iron and iron-binding protein levels. The highest iron levels were found in the liver (52 mmol/kg dry weight) and brain (49 mmol/kg dry weight) tissues. CONCLUSIONS: The distribution of iron and iron-binding proteins between the maternal and embryo-placental compartments in the first trimester is comparable to that found later in gestation, suggesting that placental iron transfer may occur as early as tertiary villi are formed. The exocoelomic fluid is probably the main iron reservoir in early pregnancy, and the secondary yolk sac is probably the principal route of entry of iron to the embryo.
OBJECTIVE: To evaluate the relation between the development of the uteroplacental circulation as assessed by Doppler velocimetry and the maternal blood relaxin concentration. METHODS: Transvaginal color Doppler investigation of the uteroplacental circulation was performed in 42 healthy women at 6-15 weeks' gestation before termination of pregnancy for psychosocial reasons. The resistance index (RI), pulsatility index (PI), and maximum peak velocity were recorded at the level of the main uterine artery, and the presence of intervillous flow was noted. Relaxin, hCG, 17 beta-estradiol (E2), and progesterone levels were measured in maternal venous blood. RESULTS: Limited intervillous flow was noted from 10 weeks' gestation and continuous intervillous flow from 12 weeks. An inverse relation was observed between the circulating levels of both E2 and progesterone and uterine artery RI and PI, whereas the relaxin level correlated positively with uterine RI and PI. Estradiol and progesterone levels also correlated positively with uterine peak systolic velocity and intervillous blood flow. Multiple linear regression analysis indicated that both hormones contributed to the decrease in downstream resistance to uterine blood flow with advancing gestational age, as assessed by uterine RI. In addition, relaxin contributed to the uterine RI and PI and to the intervillous blood flow. CONCLUSION: These data suggest that relaxin, E2, and progesterone may influence the changes in uterine blood flow that occur in early pregnancy. The role played by E2 and progesterone in the development of the uteroplacental circulation may be modulated by relaxin, constituting a novel function for this ovarian peptide.
Chorionic villus sampling and amniocentesis have disadvantages. In 100 women undergoing termination of pregnancy, coelomic fluid was successfully aspirated in 96% of cases at 6-10 weeks' gestation, 42% at 11, and 10% at 12 weeks. Cytogenetic analysis always failed with coelomic fluid, but fetal sexing was always successful with fluorescence in-situ hybridisation and polymerase chain reaction, and the results agreed with those obtained from chorionic villi and amniotic fluid in all cases. Coelocentesis may be suitable for prenatal diagnosis in the first trimester.
Biochemical analysis including concentrations of urea, creatinine, human chorionic gonadotrophin (HCG), oestradiol, progesterone, and alpha-fetoprotein (AFP), two-dimensional gel electrophoresis, and the affinity of AFP for Concanavalin A (Con A)-Sepharose were performed on samples of exocoelomic and amniotic fluids retrieved by transvaginal puncture and maternal serum from 25 normal pregnancies between 5 and 12 weeks of gestation. Biochemical assays showed that during this period of gestation no differences in urea concentration were found between fluids from the three compartments, whereas creatinine concentration decreased significantly (P < 0.001) from maternal serum to amniotic fluid. The exocoelomic fluid contained significantly (P < 0.001) higher concentrations of oestradiol, progesterone and HCG than both maternal serum and amniotic fluid. AFP concentration was similar in amniotic and exocoelomic fluids and significantly (P < 0.001) lower in maternal serum. Between the second and the third months of gestation, urea concentration decreased significantly (P < 0.05) and oestradiol, HCG and AFP increased significantly in maternal serum (P < 0.05, P < 0.05, P < 0.001, respectively). During the same period of gestation, exocoelomic fluid concentrations of urea and HCG decreased significantly (P < 0.005, P < 0.001, respectively). Comparison of the two-dimensional gel patterns obtained from maternal serum with those from exocoelomic amniotic fluids revealed no significant qualitative differences, except for several small proteins. These results suggest that protein pathways across materno-embryonic membranes are not simply passive transfers.(ABSTRACT TRUNCATED AT 250 WORDS)
Transfer of maternal thyroxine (T4) to the human fetus near term has recently been demonstrated. We investigated whether maternal thyroid hormone is available to the conceptus during the first trimester of pregnancy as well. Transvaginal ultrasound-guided puncture of the embryonic cavities was performed during the first trimester of pregnancy to obtain coelomic fluid between 6 and 11 weeks, and amniotic fluid between 8 and 11 weeks of pregnancy. T4 was found in coelomic fluid with mean values (+/- SEM) being 961 +/- 193 pmol T4/L (747 +/- 150 pg/mL). Concentrations increased both with gestational age and with rising maternal serum T4. Concentrations of 3,5,3'-triiodothyronine (T3) were at least 30 times lower, and those of 3,3',5'-triiodothyronine (rT3) four times higher, than coelomic fluid T4. Thyroxine and rT3 in amniotic fluid (8-11 weeks) were markedly lower than in the coelomic fluid, and T3 was undetectable. These results show that maternal thyroxine can cross the placental barrier as early as the second month of pregnancy. T4 from the coelomic fluid may reach the embryo via the yolk sac. This finding raises the possibility that the increase in maternal T4 occurring during the first trimester may be functionally important for the developing embryo, when its thyroid is not yet functioning.
OBJECTIVE: To assess intrafollicular blood flow in relation to ovarian morphology and function during the periovulatory period. DESIGN: A prospective, longitudinal study of random, natural ovarian cycles. SETTING: The Ovarian Screening Clinic and Endocrine Laboratory of the Department of Obstetrics and Gynaecology, King's College Hospital, London, United Kingdom. PATIENTS: Women with apparently normal ovarian function awaiting treatment for infertility by IVF-ET during subsequent natural cycles. INTERVENTIONS: All women were examined by transvaginal ultrasonography with color flow imaging and had a sample of peripheral venous blood taken at each scan for hormone analysis. MAIN OUTCOME MEASURES: The minimum pulsatility index (PI) and maximum peak systolic velocity from vessels within the dominant follicle; the maximum follicular diameters (and hence volume); serum FSH, E2, LH, and P. RESULTS: The dominant follicle ruptured in 10 of 11 women. The median interval between the two scans that delineated the time of follicular rupture was 9.5 hours (range, 0.0 to 24.5 hours). These cycles appeared to be morphologically and endocrinologically normal. There was an apparent increase in intrafollicular blood flow over the periovulatory period with an insignificant trend toward lower values for the mean PI and a significant increase in the peak systolic velocity. These changes appeared to follow the rise in circulating LH. CONCLUSION: Indexes of blood flow at a given site within the leading follicle can be monitored by transvaginal ultrasonography with color Doppler imaging over the periovulatory period. The increase in the peak systolic velocity and the relatively constant PI suggest a marked increase in blood flow at this time during the ovarian cycle.
Color Doppler was used to study the placental circulations of 28 pregnancies between 10 and 17 weeks' gestation. A histomorphometric investigation was performed on placental tissue samples from those pregnancies, and the results were compared with Doppler features. Important changes were found around 14 weeks' gestation in both uterine and umbilical circulations. The appearance of end-diastolic frequencies in the umbilical arteries was related to an abrupt and significant (p less than 0.005) increase in uterine velocity and to the establishment of a continuous intervillous circulation.
A transvaginal colour and pulsed Doppler study was performed on 44 women with normal pregnancies between 5 and 16 weeks of gestation. Maternal levels of human chorionic gonadotrophin (HCG), free alpha-HCG subunit, free beta-HCG subunit, 17 beta-oestradiol and progesterone were determined in sera obtained at the time of Doppler examination. Uterine peak systolic velocity (PSV) and alpha-HCG and 17 beta-oestradiol levels increased significantly (P < 0.001) from the second to the fourth month of gestation, whereas uterine and spiral resistance index (RI) decreased significantly (P < 0.005 and P < 0.001, respectively) with gestational age. Levels of HCG and beta-HCG peaked significantly (P < 0.01) during the third month of gestation. Corpus luteum PSV and RI and progesterone levels did not vary significantly with gestational age. Multiple regression analysis showed that gestational age was the only significant (P < 0.05) contributor to uterine PSV and spiral RI variability. In addition to gestational age, 17 beta-oestradiol had a significant (P < 0.001) influence on uterine RI. Both corpus luteum PSV and RI were significantly (P < 0.01 and P < 0.05, respectively) related to progesterone levels. Corpus luteum PSV was also significantly (P < 0.05) related to 17 beta-oestradiol levels and RI to HCG levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Exocoelomic and amniotic fluids were obtained by selective puncture under ultrasound guidance in normal human pregnancies between 5 and 13 weeks of gestation. Evaluation of the protein patterns in the exocoelomic fluid showed qualitative and quantitative changes with advancing gestation. During the second month of gestation, three electrophoretic bands were found with mobility compatible with albumin, alpha 1-globulin and beta-globulin and composed of at least eight proteins including: pre-albumin, albumin, alpha-fetoprotein (alpha-FP), alpha 1-protease inhibitor, haptoglobin, ceruloplasmin, transferrin and immunoglobulin-G, as revealed by immunoblotting. Protein patterns obtained between 9 and 13 weeks were comparable in exocoelomic fluid and in maternal serum except for the presence of alpha-FP in the alpha 1-globulin band. At the same gestational age, protein electrophoresis of amniotic fluid revealed four bands corresponding to albumin, alpha-FP, haptoglobin and transferrin. Creatinine levels were significantly lower (P less than 0.01) in amniotic fluid than in exocoelomic fluid, and alpha-FP levels were similar in both exocoelomic and amniotic fluids. These results suggest that the exocoelomic fluid is a transudate of the maternal serum except for the presence of high levels of alpha-FP, that amniotic and exocoelomic cavities are separated by a non-permeable membrane and that the secondary yolk sac plays an important role in early protein synthesis and transfer.
OBJECTIVE: To compare Doppler indices of blood flow in the uterine and spiral arteries and the corpus luteum (CL), in ectopic and intrauterine pregnancies (IUPs). DESIGN: A prospective study of women with an ectopic or singleton IUP at the corresponding stage of gestation. SETTING: The Gynaecological Ultrasound Clinic, King's College Hospital. PATIENTS: Fifty-two women, 19 with an ectopic pregnancy (EP) and 33 with an IUP. INTERVENTIONS: All women were examined by transvaginal ultrasonography with color Doppler immediately before surgery. MAIN OUTCOME MEASURES: The resistance index from the left and right uterine arteries, the spiral arteries, and the CL. The peak blood velocity (cm/sec) from the uterine arteries. The length of gestation. RESULTS: Fetal heart activity was observed in all cases of IUP at 5 weeks' gestation. Three women had an EP with a live embryo, 5 had an embryo with no heart activity, 5 contained only a yolk sac, and 2 had an empty sac. A hematocele was seen in 3 women, and 1 had tubal thickening. The mean uterine and spiral arterial resistance index decreased with the gestational age of IUPs but remained constant during EPs. Peak blood velocity in the uterine arteries increased with the gestational age of IUPs, and the values were significantly higher than in EPs. A CL was seen in 88% of women with an IUP and in 100% of women with an EP. The resistance index was similar in CL associated with both types of pregnancy, and the values did not change with gestational age. CONCLUSION: These data show that: (1) blood flow impedance in the uterine and spiral arteries, and CL, is similar in IUPs and EPs and (2) peak flow velocity in the uterine arteries reflects a decreased blood supply to EPs.
We are using transvaginal ultrasonography with color Doppler imaging to study changes in intrafollicular blood flow over the periovulatory period. We report here the findings from one volunteer (subject 9), who took two tablets of paracetamol (1000 mg) twice daily (between 07.00 and 08.00, and 18.00 and 19.00) for 2 consecutive menstrual cycle days (12 and 13) to alleviate a headache, which was shown retrospectively to have occurred within the duration of the luteinizing hormone (LH) surge in peripheral plasma. The drug appeared to have a profound effect on peak systolic blood velocity within the preovulatory follicle. Color (an index of blood velocity) disappeared and flow velocity waveforms were not detectable for at least 4 h. Color then re-appeared, but the peak systolic blood velocity had reduced by 69.8% (from 18.2 to 5.5 cm/s). The peak systolic blood velocity recovered subsequently to 16.3 cm/s, but the follicle did not rupture and continued to grow to a maximum diameter > 59 mm. There was no apparent effect of the drug on expected changes in the circulating levels of estradiol, LH, follicle stimulating hormone or progesterone. The secretory phase of the menstrual cycle lasted 13 days (i. e. day of LH peak to day of next menses minus one). We suggest that paracetamol taken at the time of the LH surge may affect intrafollicular peak systolic blood velocity and might inhibit ovulation. Possible molecular mechanisms are discussed.
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The perinatal findings of a pregnancy complicated by an umbilical cord abnormality associated with a small omphalocele are presented. The lesion was first observed at 18 weeks of gestation and was associated with elevated maternal serum alpha-fetoprotein. Serial ultrasound examinations showed major changes in the cord appearances and an associated small omphalocele was identified during the third trimester. Colour flow imaging showed no blood flow within the lesion and no obstruction nor involvement of the main umbilical vessels. Postnatal investigations demonstrated focal myxoid degeneration of the cord, a small omphalocele and no other fetal abnormalities.
Transvaginal ultrasonography with color flow mapping has been used to study changes in intrafollicular blood flow and morphology during follicular rupture and presumed ovulation in one human volunteer. Detailed monitoring started on day 11 of the menstrual cycle and the follicle began to rupture at 14.30 on day 13. This event was preceded by a defined rise and peak in the level of immunoreactive serum luteinizing hormone (LH) by 42 h and 17 h 20 min, respectively. Blood vessels were clearly visible in the inner ring of the follicle (the granulosa layer) at the time of the LH peak and part of the granulosa (probably containing the oocyte) started to detach before the follicle ruptured. The maximum value for the peak blood velocity in the inner vessels was observed 10 s after the start of follicular rupture and there was a concurrent increase in the impedance to blood flow, as reflected by the resistance index and the pulsatility index. The follicle took 14 min 29 s to empty and the corpus haemorrhagicum started to form about 1 min later. These preliminary data suggest that intrafollicular angiogenesis and changes in blood flow can be monitored by a relatively non-invasive technique. Changes in vascularity might be used to predict imminent ovulation and could possibly be identified or modified biochemically to help achieve or avoid a pregnancy.
The placental circulations of 25 normal and five complicated pregnancies were studied by color Doppler ultrasonography. Flow velocity waveforms were obtained in all 30 pregnancies and could discriminate between fetal and maternal intraplacental blood flow. We believe that color Doppler ultrasonography will improve our understanding of the pathophysiology of various pregnancy disorders that alter the placental circulations and that color ultrasonography is useful for the prenatal differential diagnosis of intrauterine masses.